Genetic Variant ZNF419:c.34-3T>C (chr19-57490144-T-C) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_024691.4(ZNF419):c.34-3T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000299 in 1,612,506 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00026 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00030 ( 0 hom. )

Consequence

ZNF419
NM_024691.4 splice_region, intron

Scores

Splicing: ADA: 0.00003186

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.627

Publications

13 publications found

Variant links:

Genes affected

ZNF419 (HGNC:20648): (zinc finger protein 419) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF419 links:

ENSG00000268107 (HGNC:):

ENSG00000268107 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024691.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
ZNF419	NM_024691.4	MANE Select	c.34-3T>C	splice_region intron	N/A	NP_078967.3
ZNF419	NM_001291744.2		c.-138T>C	5_prime_UTR	Exon 2 of 4	NP_001278673.1
ZNF419	NM_001098491.2		c.34-3T>C	splice_region intron	N/A	NP_001091961.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
ZNF419	ENST00000221735.12	TSL:1 MANE Select	c.34-3T>C	splice_region intron	N/A	ENSP00000221735.7
ZNF419	ENST00000424930.6	TSL:1	c.34-3T>C	splice_region intron	N/A	ENSP00000388864.1
ZNF419	ENST00000523439.1	TSL:1	n.265-1327T>C	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.000257

AC:

AN:

151832

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000533

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000250

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000121

AC:

AN:

247636

AF XY:

0.000104

show subpopulations

Gnomad AFR exome

AF:

0.000519

Gnomad AMR exome

AF:

0.0000584

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000178

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000303

AC:

443

AN:

1460674

Hom.:

Cov.:

AF XY:

0.000296

AC XY:

215

AN XY:

726494

show subpopulations

African (AFR)

AF:

0.000926

AC:

AN:

33478

American (AMR)

AF:

0.0000673

AC:

AN:

44606

Ashkenazi Jewish (ASJ)

AF:

0.0000383

AC:

AN:

26104

East Asian (EAS)

AF:

0.00

AC:

AN:

39684

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86000

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53350

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.000350

AC:

389

AN:

1111350

Other (OTH)

AF:

0.000298

AC:

AN:

60340

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

101

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000257

AC:

AN:

151832

Hom.:

Cov.:

AF XY:

0.000243

AC XY:

AN XY:

74108

show subpopulations

African (AFR)

AF:

0.000533

AC:

AN:

41310

American (AMR)

AF:

0.00

AC:

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5142

South Asian (SAS)

AF:

0.00

AC:

AN:

4808

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10564

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.000250

AC:

AN:

67974

Other (OTH)

AF:

0.00

AC:

AN:

2082

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.516

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000897

Hom.:

1072

EpiCase

AF:

0.000109

EpiControl

AF:

0.000238

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

1.0

(source)

DANN

Benign

0.54

PhyloP100

-0.63

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000032

dbscSNV1_RF

Benign

0.0

SpliceAI score (max)

0.070

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over